LIVER-FUNCTION AND MORPHOLOGY AFTER RESUSCITATION FROM SEVERE HEMORRHAGE SHOCK WITH HEMOGLOBIN-SOLUTIONS OR AUTOLOGOUS BLOOD

Objective: To test the effects of three hemoglobin solutions on liver function and hepatic morphology after resuscitation from severe hemorr hagic shock. Design: Prospective study. Setting: Laboratory. Subjects: Thirty-three beagle dogs. Intervention: Hemorrhagic shock was induced in anesthetized dogs by removal of blood at a rate of 2 mL/kg/min unt il systolic blood pressure (BP) reached 50 mm Hg. BP was maintained at this level for 2 hrs by further withdrawing 5 to 10 mL aliquots whene ver BP increased >50 mm Hg. Resuscitation was then initiated with auto logous whole blood (n = 7), 4% pyridoxalated-hemoglobin-polyoxyethylen e conjugate (4% PHP [n = 6]), 8% pyridoxalated-hemoglobin-polyoxyethyl ene conjugate (8% PHP [n = 9]), or 8% stroma-free hemoglobin (n = 7). Four dogs were managed identically but were not resuscitated. Gross ne cropsy and histologic examination of the liver were performed on all d ogs after 7 days, or earlier if death occurred. Measurements and Main Results: In vitro interferences of PHP and stroma-free hemoglobin with liver function tests were determined and recommendations for interpre tation of results from blood samples containing PHP and stroma-free he moglobin were made. Blood was collected before, during, and after resu scitation from hemorrhagic shock. The dogs were then awakened and surv ivors were monitored daily with blood sampling until they were killed and necropsy was performed. After 7 days, the survival rate following hemorrhagic shock was 100% for whole blood and 4% PHP, 86% for stroma- free hemoglobin, and 33% for 8% PHP. Of the resuscitated dogs not surv iving 7 days, all but one died within 27 hrs from coagulopathy. All do gs not resuscitated died within 1.75 hrs after 2 hrs of shock. Bilirub in, alkaline phosphatase, and lactic dehydrogenase concentrations coul d not be measured due to interferences of stroma-free hemoglobin and P HP. Aspartate (AsT) and alanine (ALT) aminotransferase concentrations could be measured after dilution to overcome the interferences. Signif icant increases in AST and ALT values in all groups 24 hrs after resus citation were attributed to hypoxic hepatocellular damage associated w ith the severity of the shock model rather than to the resuscitation f luid. Liver histology showed no changes attributed to toxic damage of hepatocytes in dogs resuscitated with stroma-free hemoglobin or PHP. H owever, the histologic changes, particularly hepatocellular hydropic c hanges, were less severe in dogs resuscitated with 4% PHP than in othe r groups. Conclusion: Morphologic studies at necropsy and liver functi on tests in dogs receiving hemoglobin solutions, compared with autolog ous blood, support the conclusion that the PHP and stroma-free hemoglo bin solutions tested did not produce hepatic toxicity when used as res uscitation fluids in this model of severe shock.